Fteah Asmaa Mohamed, Ahmed Asmaa Ismail, Mosaad Nehad Ahmed, Hassan Mona Mohamed, Mahmoud Sherif Hamdy
Department of Clinical and Chemical Pathology, Theodor Bilharz Research Institute, Egypt.
Department of Clinical and Chemical Pathology, Kasr Al-Ainy, Faculty of Medicine, Cairo University, Egypt.
Asian Pac J Cancer Prev. 2019 Nov 1;20(11):3479-3485. doi: 10.31557/APJCP.2019.20.11.3479.
Hepatocellular carcinoma (HCC) is the commonest primary tumor of the liver. Chronic HCV infection is the leading cause of end-stage liver disease, HCC and liver-related death in Egypt. Single nucleotide polymorphisms (SNPs) in microRNAs were reported to increase susceptibility to tumorigenesis; affect prognosis and as promising biomarkers in virus-host interactions. This study was conducted to investigate the role of genetic variants of miR-196a2 (rs 11614913) C>T and miR-499 (rs 3746444) A>G in the development of cirrhosis and HCC in Egyptian HCV infected patients. Genotyping of the candidate SNPs was performed by Real Time PCR in 75 HCV-related HCC patients, 75 cirrhotic patients on top of HCV and 75 healthy controls. There was significant difference in miR-499 (rs3746444) genotypes frequency between the three studied groups as the GG genotype was significantly lower in HCC cases than other groups (P = 0.009) while the combined miR-499 (AA+AG) genotypes were significantly higher in HCC cases than other groups (P = 0.005). Also a significant difference was found in miR-499 genotypes frequency when compared between HCC and cirrhosis groups as the GG genotype was significantly lower in HCC cases than cirrhosis group (P = 0.006) while the combined miR-499 (AA+AG) genotypes were significantly higher in HCC cases than in cirrhosis group (P = 0.003) [OR (95% CI) = 0.131 (0.028-0.601)]. The frequency of the G allele was significantly lower in HCC than other groups (P = 0.024) and significantly lower in HCC than normal group (P = 0.006) [OR (95%CI) = 0.501 (0.304-0.825)]. For miR-196a2 (rs11614913) C>T polymorphisms, no significant association was found with HCC risk. Our study concluded that the G allele of miR-499 is associated with lower risk of HCV related HCC development. No significant association of miR-196a2 (rs 11614913), genotypes or alleles with risk for HCC development, could be detected.
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肝细胞癌（HCC）是最常见的原发性肝脏肿瘤。慢性丙型肝炎病毒（HCV）感染是埃及终末期肝病、HCC及肝脏相关死亡的主要原因。据报道，微小RNA中的单核苷酸多态性（SNP）会增加肿瘤发生易感性；影响预后，并有望成为病毒-宿主相互作用中的生物标志物。本研究旨在调查miR-196a2（rs 11614913）C>T和miR-499（rs 3746444）A>G的基因变异在埃及HCV感染患者肝硬化和HCC发生中的作用。通过实时聚合酶链反应（Real Time PCR）对75例HCV相关HCC患者、75例HCV合并肝硬化患者及75例健康对照者进行候选SNP基因分型。在三个研究组中，miR-499（rs3746444）基因型频率存在显著差异，因为HCC病例中的GG基因型显著低于其他组（P = 0.009），而HCC病例中miR-499（AA+AG）合并基因型显著高于其他组（P = 0.005）。此外，比较HCC组和肝硬化组时，miR-499基因型频率也存在显著差异，因为HCC病例中的GG基因型显著低于肝硬化组（P = 0.006），而HCC病例中miR-499（AA+AG）合并基因型显著高于肝硬化组（P = 0.003）[比值比（95%可信区间）= 0.131（0.028 - 0.601）]。HCC中G等位基因频率显著低于其他组（P = 0.024），且显著低于正常组（P = 0.006）[比值比（95%可信区间）= 0.501（0.304 - 0.825）]。对于miR-196a2（rs11614913）C>T多态性，未发现与HCC风险有显著关联。我们的研究得出结论，miR-499的G等位基因与HCV相关HCC发生风险较低有关。未检测到miR-196a2（rs 11614913）的基因型或等位基因与HCC发生风险有显著关联。
